Meta-analysis of the predictive and prognostic value of erlotinib-related biomarkers in phase III, placebo-controlled trials in non-small cell lung cancer (NSCLC): Recommendations of the BioLOGUE advisors.

Abstract

7533 Background: The BioLOGUE (Biomarkers Lung Oncology Group Understanding Erlotinib) advisors carried out a meta-analysis using two phase III, placebo-controlled trials of erlotinib to determine the clinical utility of four tumor-based biomarkers (BMs) in the post-first line setting: EGFR protein expression (immunohistochemistry [IHC]); EGFR copy number (fluorescent in-situ hybridization [FISH]); EGFR activating mutations; and KRAS mutations. Methods: Patient-based data from BR.21 and SATURN were pooled to carry out univariate and multivariate analyses of PFS and OS, with or without clinical factors, which differentiated between predictive and prognostic effects. Stepwise variable selection was used to identify any confounding relationships between BMs, clinical factors and outcome. Full methodology will be presented. Results: Results of the pooled meta-analysis for each BM are shown in the table: X indicates a predictive effect for outcome with erlotinib, Y+ and Y- indicate a positive or negative prognostic effect, respectively, and x or y indicate a trend, i.e. 0.05 < p ≤0.10. Conclusions: Based on these analyses, EGFR IHC, EGFR FISH and KRAS mutations should not be used to positively or negatively select patients for erlotinib after first-line chemotherapy. EGFR mutation testing, while of value in the first-line setting, should not be used to positively or negatively select patients for maintenance/second-line erlotinib. PFS OS Cox model terms EGFR IHC EGFR FISH EGFR mut KRAS mut EGFR IHC EGFR FISH EGFR mut KRAS mut BM only Y+ p=0.0210 HR=1.19 X p=0.0442 X p=0.0480 Y- p=0.0004 HR=1.43 – – Y+ p < 0.0001 HR=0.53 Y-p=0.0349 HR=1.27 BM and patient chars Y+ p=0.0122 HR=1.21 x p=0.0540 X p=0.0293 Y- p=0.0021 HR=1.37 y+ p=0.0669 HR=1.17 – Y+ p=0.0054 HR=0.65 Y- p=0.0931 HR=1.21 BM and other BMs Y+ p=0.0171 HR=1.20 – x p=0.0614 Y- p=0.0010 HR=1.40 – – Y+ p < 0.0001 HR=0.54 y- p=0.0810 HR=1.22 BM and other BMs and patient chars Y+ p=0.0050 HR=1.24 – X p=0.0371 Y- p=0.0030 HR=1.36 y+ p=0.0835 HR=1.26 – Y+ p=0.0049 HR=0.64 y- p=0.0803 HR=1.22